Modulation of phenolic metabolism under stress conditions in a Lotus japonicus mutant lacking plastidic glutamine synthetase

This paper was aimed to investigate the possible implications of the lack of plastidic glutamine synthetase (GS2) in phenolic metabolism during stress responses in the model legume Lotus japonicus. Important changes in the transcriptome were detected in a GS2 mutant called Ljgln2-2, compared to the wild type, in response to two separate stress conditions, such as drought or the result of the impairment of the photorespiratory cycle. Detailed transcriptomic analysis showed that the biosynthesis of phenolic compounds was affected in the mutant plants in these two different types of stress situations. For this reason, the genes and metabolites related to this metabolic route were further investigated using a combined approach of gene expression analysis and metabolite profiling. A high induction of the expression of several genes for the biosynthesis of different branches of the phenolic biosynthetic pathway was detected by qRT-PCR. The extent of induction was always higher in Ljgln2-2, probably reflecting the higher stress levels present in this genotype. This was paralleled by accumulation of several kaempferol and quercetine glycosides, some of them described for the first time in L. japonicus, and of high levels of the isoflavonoid vestitol. The results obtained indicate that the absence of GS2 affects different aspects of phenolic metabolism in L. japonicus plants in response to stress.España FEDER-Ministerio de Economía y Competitividad AGL2014-54413-REspaña Junta de Andalucía,Consejería de Economía, Innovación y Ciencia, P1O-CVI-6368España Junta de Andalucía,Consejería de Economía, Innovación y Ciencia, BIO-16

Spectral Assignment in the [3 + 2] Cycloadditions of Methyl (2<i>E</i>)-3-(Acridin-4-yl)-prop-2-enoate and 4-[(<i>E</i>)-2-Phenylethenyl]acridin with Unstable Nitrile N-Oxides

The investigation of cycloaddition reactions involving acridine-based dipolarophiles revealed distinct regioselectivity patterns influenced mainly by the electronic factor. Specifically, the reactions of methyl-(2E)-3-(acridin-4-yl)-prop-2-enoate and 4-[(1E)-2-phenylethenyl]acridine with unstable benzonitrile N-oxides were studied. For methyl-(2E)-3-(acridin-4-yl)-prop-2-enoate, the formation of two regioisomers favoured the 5-(acridin-4-yl)-4,5-dihydro-1,2-oxazole-4-carboxylates, with remarkable exclusivity in the case of 4-methoxybenzonitrile oxide. Conversely, 4-[(1E)-2-phenylethenyl]acridine displayed reversed regioselectivity, favouring products 4-[3-(substituted phenyl)-5-phenyl-4,5-dihydro-1,2-oxazol-4-yl]acridine. Subsequent hydrolysis of isolated methyl 5-(acridin-4-yl)-3-phenyl-4,5-dihydro-1,2-oxazole-4-carboxylates resulted in the production of carboxylic acids, with nearly complete conversion. During NMR measurements of carboxylic acids in CDCl3, decarboxylation was observed, indicating the formation of a new prochiral carbon centre C-4, further confirmed by a noticeable colour change. Overall, this investigation provides valuable insights into regioselectivity in cycloaddition reactions and subsequent transformations, suggesting potential applications across diverse scientific domains

Zinc( ii ) and cadmium( ii ) amorphous metal–organic frameworks (aMOFs): study of activation process and high-pressure adsorption of greenhouse gases

International audienceTwo novel amorphous metal–organic frameworks UPJS-13 and UPJS-14 , constructed of Zn( ii )/Cd( ii ) ions and extended tetrahedral linker were prepared, characterised and applied as adsorbents for carbon dioxide and methane

The Induction of G2/M Phase Cell Cycle Arrest and Apoptosis by the Chalcone Derivative 1C in Sensitive and Resistant Ovarian Cancer Cells Is Associated with ROS Generation

Ovarian cancer ranks among the most severe forms of cancer affecting the female reproductive organs, posing a significant clinical challenge primarily due to the development of resistance to conventional therapies. This study investigated the effects of the chalcone derivative 1C on sensitive (A2780) and cisplatin-resistant (A2780cis) ovarian cancer cell lines. Our findings revealed that 1C suppressed cell viability, induced cell cycle arrest at the G2/M phase, and triggered apoptosis in both cell lines. These effects are closely associated with generating reactive oxygen species (ROS). Mechanistically, 1C induced DNA damage, modulated the activity of p21, PCNA, and phosphorylation of Rb and Bad proteins, as well as cleaved PARP. Moreover, it modulated Akt, Erk1/2, and NF-κB signaling pathways. Interestingly, we observed differential effects of 1C on Nrf2 levels between sensitive and resistant cells. While 1C increased Nrf2 levels in sensitive cells after 12 h and decreased them after 48 h, the opposite effect was observed in resistant cells. Notably, most of these effects were suppressed by the potent antioxidant N-acetylcysteine (NAC), underscoring the crucial role of ROS in 1C-induced antiproliferative activity. Moreover, we suggest that modulation of Nrf2 levels can, at least partially, contribute to the antiproliferative effect of chalcone 1C

Mechanochemical Synthesis and Isomerization of N-Substituted Indole-3-carboxaldehyde Oximes †

Performing solution-phase oximation reactions with hydroxylamine hydrochloride (NH2OH&middot;HCl) carries significant risk, especially in aqueous solutions. In the present study, four N-substituted indole-3-carboxaldehyde oximes were prepared from the corresponding aldehydes by solvent-free reaction with NH2OH&middot;HCl and a base (NaOH or Na2CO3) using a mechanochemical approach, thus minimizing the possible risk. In all cases, the conversion to oximes was almost complete. The focus of this work is on 1-methoxyindole-3-carboxaldehyde oxime, a key intermediate in the production of indole phytoalexins with useful antimicrobial properties. Under optimized conditions, it was possible to reach almost 95% yield after 20 min of milling. Moreover, for the products containing electron-donating substituents (-CH3, -OCH3), the isomerization from the oxime anti to syn isomer under acidic conditions was discovered. For the 1-methoxy analog, the acidic isomerization of pure isomers in solution resulted in the formation of anti isomer, whereas the prevalence of syn isomer was observed in solid state. From NMR data the syn and anti structures of produced oximes were elucidated. This work shows an interesting and possibly scalable alternative to classical synthesis and underlines environmentally friendly and sustainable character of mechanochemistry

A Comparative Study of Isolated Secondary Metabolites from Lichens and Their Antioxidative Properties

Free radicals play a critical role in the chemical processes that occur in all cells. Pharmaceutical companies manufacture a variety of synthetically prepared antioxidants, but it is known that many of these can be carcinogenic. As a result, efforts are being made to find natural antioxidants that do not have these side effects. Lichens may be suitable candidates because they contain secondary metabolites with proven antioxidant properties. This could be explained by the presence of compounds with phenolic groups in lichens. The radical scavenging reaction is a chemical reaction governed by stoichiometry, and our aim is to determine the efficacy of these reactions. The aim of this study is to compare metabolite activity based on the same amount of substance involved in radical scavenging, calculated in micromoles rather than weight concentration. This provides an accurate way of comparing radical scavenging activity. We tested superoxide anion scavenging activity and free radical scavenging activity of isolated lichen secondary metabolites and their mixtures in different ratios. The following compounds were isolated and tested for antioxidant activity: gyrophoric acid (Umbilicaria hirsuta), evernic acid (Evernia prunastri), physodic acid, 3-hydroxyphysodic acid, physodalic acid and atranorin (Hypogymnia physodes), and usnic acid (as a synthetic compound). Of all the tested compounds, 3-hydroxyphysodic acid, as well as mixtures containing this metabolite, showed the strongest scavenging activity. The results also demonstrated that calculation by amount of substance leads to a new consideration of antioxidant activity

Design, Synthesis, and Evaluation of Novel Indole Hybrid Chalcones and Their Antiproliferative and Antioxidant Activity

The synthesis, anticancer, and antioxidant activities of a series of indole-derived hybrid chalcones are reported here. First, using the well-known Claisen–Schmidt condensation method, a set of 29 chalcones has been designed, synthesized, and consequently characterized. Subsequently, screening for the antiproliferative activity of the synthesized hybrid chalcones was performed on five cancer cell lines (HCT116, HeLa, Jurkat, MDA-MB-231, and MCF7) and two non-cancer cell lines (MCF-10A and Bj-5ta). Chalcone 18c, bearing 1-methoxyindole and catechol structural features, exhibited selective activity against cancer cell lines with IC50 values of 8.0 ± 1.4 µM (Jurkat) and 18.2 ± 2.9 µM (HCT116) and showed no toxicity to non-cancer cells. Furthermore, antioxidant activity was evaluated using three different methods. The in vitro studies of radical scavenging activity utilizing DPPH radicals as well as the FRAP method demonstrated the strong activity of catechol derivatives 18a–c. According to the ABTS radical scavenging assay, the 3-methoxy-4-hydroxy-substituted chalcones 19a–c were slightly more favorable. In general, a series of 3,4-dihydroxychalcone derivatives showed properties as a lead compound for both antioxidant and antiproliferative activity

A Comparative Study of Isolated Secondary Metabolites from Lichens and Their Antioxidative Properties

Free radicals play a critical role in the chemical processes that occur in all cells. Pharmaceutical companies manufacture a variety of synthetically prepared antioxidants, but it is known that many of these can be carcinogenic. As a result, efforts are being made to find natural antioxidants that do not have these side effects. Lichens may be suitable candidates because they contain secondary metabolites with proven antioxidant properties. This could be explained by the presence of compounds with phenolic groups in lichens. The radical scavenging reaction is a chemical reaction governed by stoichiometry, and our aim is to determine the efficacy of these reactions. The aim of this study is to compare metabolite activity based on the same amount of substance involved in radical scavenging, calculated in micromoles rather than weight concentration. This provides an accurate way of comparing radical scavenging activity. We tested superoxide anion scavenging activity and free radical scavenging activity of isolated lichen secondary metabolites and their mixtures in different ratios. The following compounds were isolated and tested for antioxidant activity: gyrophoric acid (Umbilicaria hirsuta), evernic acid (Evernia prunastri), physodic acid, 3-hydroxyphysodic acid, physodalic acid and atranorin (Hypogymnia physodes), and usnic acid (as a synthetic compound). Of all the tested compounds, 3-hydroxyphysodic acid, as well as mixtures containing this metabolite, showed the strongest scavenging activity. The results also demonstrated that calculation by amount of substance leads to a new consideration of antioxidant activity